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for the Study of the
One Side of the Background to an Academic Freedom Dispute
by David Healy
the guest speaker at the annual meeting of the British Association for
Psychopharmacology in July 2000 came up to me at a BAP poster stand, where
I was presenting details of a study, and said that I had no right to
present research like this, I was shocked.
Even when challenged with the fact that there was other unpublished
data, which amply bore out the findings and conclusions being reported, he
still insisted that I should not be presenting research like this.
Frighteningly, he went on to make it clear that he had been
approached to get involved in a set of legal actions “against me”.
study was one that was designed to explore whether antidepressants
selective to different neurotransmitter systems have different functional
effects. With colleagues, I
recruited twenty senior medical, nursing and administrative staff from the
psychiatric unit in which the North Wales University Department of
Psychiatry was also based. The
volunteers were randomized to a clinical dose of sertraline, a Selective
Serotonin Reuptake Inhibitor (trade name Zoloft) or reboxetine, an agent
selective to the norepinephrine system (not available in North America)
for two weeks, followed by a two-week discontinuation arm and then
randomization to the other agent for two weeks.
they specify functional differences between the two agents?
We had a series of other questions such as whether personality type
predicted who would prefer which agent.
The study found that drugs selective to the norepinephrine system
increased drive and energy whereas a selective serotonin reuptake
inhibitor appeared to produce a mellowing of affect.
Personality measures did predict who would prefer these
differential effects and we found that 1/3rd of our subjects
preferred the effects of sertraline while 1/3rd preferred those
of reboxetine. Roughly half
of our subjects felt better than well on one or other of the two agents.
Those who strongly preferred sertraline did rather poorly on
reboxetine and vice versa (Tranter et al 2002).
In the case of two of our volunteers the effects of sertraline were
disastrous. They became
acutely and seriously suicidal (Healy 2000a).
the time I presented these results, I was aware that our findings were not
unique. More than 15 years
beforehand Pfizer had run a study in which healthy female volunteers were
randomized to sertraline or placebo.
The study terminated early with all those receiving sertraline
discontinuing because of problems in the domain of agitation and
study had come to my attention owing to an involvement in a medico-legal
case – Miller versus Pfizer.
Matthew Miller was a 13-year old boy who following a house move had
become disruptive at his new school and had been assessed for possible
nervous problems. There were
suggestions that he might be mildly depressed.
He was given sertraline and a week later he had hung himself one
years before my involvement in the Miller case, shortly after fluoxetine
and fluvoxamine had been launched on the British market, I had written up
a pair of clinical cases in which two individuals had become suicidal
within the first weeks of treatment with fluoxetine.
The suicidality had cleared up on discontinuation of treatment but
had re-emerged when re-challenged with a further antidepressant active on
the serotonin system (Creaney et al 1991).
This had led on to a review of SSRI induced suicidality (Healy
1994), which had triggered a series of medico-legal approaches.
In all instances, I had offered the view that the SSRI involved had
not caused the problems that the plaintiffs were claiming.
picture changed in 1997 when I was approached on the case of William
Forsyth a man who after taking Prozac for 10 days had butchered his wife
and then killed himself. In
this instance the drug did seem to me to be involved.
But whereas Lilly had settled a great number of other cases prior
to this, this case went to trial and in the process I became aware of an
increasing number of documents and data from within Lilly and elsewhere,
which reinforced my views that SSRIs could cause problems (Healy 1999a).
The Forsyth case led to involvement in the Miller, Motus and Tobin
cases. Miller and Motus
involved sertraline and Pfizer, while Tobin involved paroxetine and Glaxo
the end of 1998, I had a first overture about a possible move from Britain
to the Center for Addiction and Mental Health (CAMH) in the University of
Toronto (formerly the Clarke Institute).
This led to interviews with the search panel in the course of 1999
and a formal university job offer, which in early 2000 I accepted.
The position was a Professor of Psychiatry in the University of
Toronto and Head of the Mood and Anxiety Disorders Program within CAMH.
Aspects of the recruitment process and visa applications led to
four visits to Toronto during the course of 1999 and 2000.
In a series of lectures, I presented research on the history of the
antidepressants (Healy 1997) as well as research indicating that Mental
Health Services in general may be doing less well than is commonly
portrayed (Healy et al 2001). In
the course of various meetings I made no secret of my involvement in the
SSRI controversies, on which I had several current publications (Healy and
Savage 1998; Healy 1999a; Healy et al 1999).
a personal front involvement in SSRI medico-legal issues made no
difference to my willingness to undertake clinical trials of psychotropic
agents or preparedness to be a consultant to pharmaceutical companies or
to lecture at company sponsored symposia or in other venues.
The problems of possible suicide induction as I saw them were ones
that could be handled with appropriate warnings and monitoring.
August 2000, I was invited to be a guest speaker at a meeting organized
for the end of November 2000 to celebrate the 75th Anniversary
of the University Department and the 150th Anniversary of the
establishment of Clinical Services in Toronto.
I agreed to talk on the topic of psychopharmacology and the
government of the self. This
talk reproduced on this website in essence gives the outlines of a then
forthcoming book from Harvard University Press – which overviewed the
emergence of psychopharmacology, the development of the field and
prospects for the future (Healy 2002).
This seemed appropriate in the context of a meeting called Looking
Back, Looking Ahead.
was due to give the same lecture the following week in Cornell Medical
School as part of the Eric T Carlsson Memorial Grand Rounds in the History
of Medicine and the Richardson Research Seminar Series.
Part of the lecture had been given previously at the invitation of
AstraZeneca. The full lecture
has subsequently been given in Paris, Minneapolis, Cambridge and
the day before the meeting in Toronto, I sat on an interview panel to
appoint a neuropsychologist who would work with me on the Mood Disorders
Program. I was consulted
about the decor of my office as well as computing support.
I discussed removal expenses and associated issues with David
Goldbloom, the Physician in Chief of the CAMH.
I mentioned my SSRI medico legal work to him, which he appeared to
view as potential departmental funds.
His only concern appeared to be to get me safely ensconced in the
University of Toronto, even earlier than I had planned to get there.
I was less than two weeks away from completing the last formalities
in the visa process.
is customary these days, the lecture in Toronto was rated for presentation
and content by the audience, an audience of over 200 people from across
the board in the Mental Health Services.
My lecture was rated highest for content.
The same lecture was very warmly received in Cornell the following
week, as it has been elsewhere since.
in the hours following the lecture, I was told that David Goldbloom had
taken exception to some of the points that had been raised.
The points that concerned him, I was told, were that I’d claimed
that Prozac could make people suicidal, that Lilly knew about it (a claim
not made) and that we were now treating more patients than ever before
(see Healy et al 2001). I
arranged to meet with Goldbloom following a celebratory meal that evening.
He was apoplectic. There
are only three points he told me that any one would ever remember from a
lecture – and in this case the points they would remember were that
Prozac makes people suicidal, that Lilly knew about it and that high dose
antipsychotics can cause brain damage.
A further charge that appeared later was that I had claimed that
very large proportions of the clinical literature were now ghost-written.
following day I left for New York. I
had a schedule, which involved spending three days in Pfizer’s New York
archives, where I wanted to look at their unpublished healthy volunteer
studies with sertraline, before lecturing in Cornell.
the lecture in Cornell there was also a meal.
At this, the Dean of the Medical School, Bob Michels, asked what
had happened in Toronto. Astonished
at the enquiry I outlined the story above.
Michels however appears to have known that the CAMH had taken the
step to rescind my job offer as they saw it; breach their contract with
me, as I was later to see it. How
had he known?
still do not know the answer to this but it turned out that that one of
the lecturers at the Toronto meeting, Dr Charles Nemeroff, attending
American Foundation for Suicide Prevention council meetings in New York
the day after the Toronto meeting had volubly raised the issues of Healy
and his views on SSRIs. It
later transpired that his lawyer, Nina Gussack, who has represented Lilly
on occasions, made it clear that Dr Nemeroff had been approached during
the day previously when he was in Toronto and had made his views on Healy
clear at that point and that he had been left with the impression that
choices had been made there and then.
I was later to find out by email that there apparently had also
been at least one phone-call to senior figures in Cornell in the days
before I lectured there, making what appear to have been extraordinary
claims and apparently suggesting the invitation be withdrawn.
the lecture in Cornell, I arrived home from New York to find an e-mail
waiting from David Goldbloom saying that:
we believe that it is not a good fit between you and the role as leader of
an academic program in mood and anxiety disorders at the Centre.
you are held in high regard as a scholar of the history of modern
we do not feel your approach is compatible with the goals for development
of the academic and clinical resource that we have.
This view was solidified by your recent appearance at the Centre in the
context of an academic lecture.”
people reading this since have read a message that Goldbloom was concerned
about pharmaceutical company monies to the University Department.
I was more struck the apparent implication that my analysis of the
situation was correct (high esteem as a historian of modern psychiatry)
but that a correct analysis was incompatible with employment in a modern
biological psychiatry oriented department.
It appeared to smack of academic totalitarianism.
it came to considering the ramifications of these events on my future
career, there was a pressing issue to be addressed.
I was at this point involved in a case, Tobin versus SmithKline,
which was due in court in Cheyenne, Wyoming, in May 2001.
I could envisage a situation where my first question on the witness
stand would be about being sacked from the University of Toronto.
Where my first instincts would probably be in line with almost
everybody else’s instincts in a situation like this, namely to lie low,
it seemed I had little option but to do something.
February 15th, I wrote to the Chair of the Ethics Committee at
CAMH suggesting that in all probability neither CAMH, nor the university,
nor I knew the full dimensions of what was happening.
For instance, I pointed out that in March 2000 there had been a
special issue on Prozac brought out by the Hasting Center Reports, in
which an article of mine called Good Science or Good Business made the
points that we were treating more people than ever before, that Prozac
could make people suicidal and that an increasing proportion of the
therapeutics literature was ghost-written (Healy 2000).
Another even earlier article had argued that antidepressants and
depression were almost unknown outside of mainstream psychiatry twenty
years previously but we were now apparently in an Age of Depression
(1999b). The antidepressant
market has in fact grown 800% by value in the 1990s and by 2000 had become
a $10 billion market.
turned out that Lilly was one of the biggest private funders of the
Hastings Center and following this article they withdrew their support.
The Hastings Center had my article re-reviewed.
One of these re-reviews said that essentially the only mistake I
had made was in not going far enough in spelling out how much of the
psychopharmacology literature was ghost written, how many of the clinical
trials being run with psychotropic compounds ended up sealed and how much
of the research was market oriented rather than designed to answer
had received a great deal of money from Lilly, SmithKline and other
companies. CBC television
were later to report that in the previous year, around 50% of the Mood
Disorders Program’s research money had come from pharmaceutical company
sources. Had this played a
part in the decision? Given
that the points of concern in my lecture were similar to the points made
in the Hastings Center article, there was a set of background issues
against which the CAMH decision to breach my contract was likely to be
judged in the wider academic domain.
Surely this provided grounds to talk before the situation got out
hope was that if they were better apprised of the dimensions of the
problem, key figures in both CAMH and the university would be interested
to meet up and try and find some solution.
I was due to speak in April at a meeting in Toronto and we could
have met then. But far from
being interested to meet, the Chair of the Ethics Committee didn’t
answer. My February letter
was answered by the Chair of the Board of Trustees in March -
turned to the Canadian Association for University Teachers who wrote to
the President of the University of Toronto expressing concerns.
The response from the President to CAUT was dismissive.
In April the issue began to run in the media in both Canada and the
Tobin case began at the end of May. Donald
Schell was a man with a history of several relatively brief episodes of
depression. He had a prior
history of an adverse response to Prozac in 1990.
He had then subsequently been put on Paxil by another physician in
1998 and 48 hours later had murdered his wife, Rita, along with his
daughter and granddaughter who were staying with Don and Rita Schell
before killing himself. His
surviving son-in-law, Tim Tobin, took out a case for wrongful death
part of my background research for this case, I had been given access to
SmithKline’s paroxetine healthy volunteer archive.
It was clear from this that paroxetine caused agitation in around
25% of takers, that it did so in a dose-dependent way and on a challenge-rechallenge
basis, and that there had been a suicide in the program.
It also caused physical dependence in one study in around 85% of
subjects (Healy 2001b).
evidence of dependence was interesting in the light of SmithKline’s
license to claim their drug was useful for the prophylaxis of depression.
This license was based on studies, which re-randomized patients to
placebo, and interpreted the subsequent problems of those re-randomized to
placebo as new illness episodes (Montgomery and Dunbar 1993).
the Tobin case, it became clear that studies had been terminated early
with their results left unpublished.
It also became clear that despite a backdrop that gave serious
grounds for concern, there had been a failure to test paroxetine or other
SSRIs for the induction of possible suicidality.
Finally, the case raised questions about how much of a company’s
defense in these SSRI cases depended on ghost-written, or company only
authored publications, or how often when there was medical testimony it
was based on tabulated figures provided to an expert rather than the raw
2000 an article by Khan and colleagues in Archives of General Psychiatry
had presented the following data from trials submitted to the FDA as part
of the license applications for a series of recently released
FDA documents (Brecher 1991; Lee 1991) revealed that some suicidal acts
categorized as occurring on placebo in this table had in fact occurred
during the washout period of clinical trials – the initial phase of
trials when prior medication is halted before the patient is randomized to
either placebo or active medication.
These gives rise to a revised table:
2: Incidence of Suicides and
Suicide Attempts in Worldwide Phase 1 -3 Investigational Antidepressant
these suicidal acts by the traditional method, in terms of absolute
numbers of patients, indicates a statistically significant excess of
suicidal acts on new antidepressants as a group compared to placebo and a
specific excess on paroxetine compared to placebo.
It also indicates that changing or withdrawing from medication can
be more risky than is commonly noted.
data also suggest something else. In
the Tobin case, the defense appealed to the same data on paroxetine that
appears in Table 1, which had previously appeared in two articles (Lopez-Ibor
1992; Montgomery et al 1995). The
failure to distinguish between placebo and washout suicidal acts suggests
that the eminent authors of these articles may not have actually seen the
raw data, which raises profound questions about the status of the
June 6th 2001, the Court came to a verdict, which found against
Glaxo SmithKline. In
September 2001, I filed an legal action for breach of academic freedom
against the University of Toronto and the Centre for Addiction and Mental
M. 1991. FDA Review &
Evaluation of Clinical Data Original NDA 20-021, Paroxetine Safety Review
W., I. Murray, and D. Healy. 1991. Antidepressant
induced suicidal ideation. Human
Psychopharmacology 6: 329‑332
D. 1994. The fluoxetine and
suicide controversy. CNS Drugs
D. 1997. The
Antidepressant Era. Cambridge
Mass: Harvard University Press.
D., and M. Savage. 1998. Reserpine
Journal of Psychiatry 172: 376-378.
D. 1999a. Guest Editorial: A Failure to Warn.
Int J Risk & Safety in
Medicine 12: 151-156.
D. 1999b. The Three Faces of the
Comments on the Clinical-Economic Framework of Diagnosis.
Journal of Nervous & Mental Disease 187: 174-180
D., C. Langmaak C., and M. Savage. 1999.
Suicide in the Course of the Treatment of Depression.
Psychopharmacology 13: 94-99.
D. 2000a. Antidepressant
induced suicidality. Primary
Care Psychiatry 6: 23-28.
Healy, D. 2000b. Good Science or Good Business? Hastings Center Report 30: 19-22.
D., M. Savage, P. Michael, M.
Harris, D. Hirst, M. Carter, D. Cattell, T. McMonagle, N. Sohler, and E.
Susser. 2001. Psychiatric bed utilisation: 1896 and 1996 compared.
D. 2001c. Trial testimony in
Tobin vs SmithKline, Cheyenne, Wyoming, May 22nd 2001.
D. 2002. The Creation
of Psychopharmacology. Cambridge
Mass: Harvard University Press.
A., H.A. Warner, and W.A. Brown, 2000.
Symptom reduction and suicide risk in patients treated with placebo
in antidepressant clinical trials. Archives
of General Psychiatry 57: 311-317.
H. 1991. Statistical reviews
on Sertraline for FDA, August 14th 1990 and January 31st
JJ. (1993). Reduced suicidality on paroxetine.
European Psychiatry 1 (Suppl 8): 17s-19s.
SA, Dunner DL, Dunbar G (1995). Reduction
of suicidal thoughts with paroxetine in comparison to reference
antidepressants and placebo. European
Neuropsychopharmacology, 5: 5-13.
S.A., and G.C. Dunbar. 1993. Paroxetine
is better than placebo in relapse prevention and the prophylaxis of
recurrent depression. International
Clinical Psychopharmacology. 8:
Tranter, R., H. Healy, D. Cattell, and D. Healy. (2002). Functional effects of agents differentially selective to noradrenergic or serotonergic systems. Psychological Medicine (in press).
Healy Qualified from University College Dublin in 1979.
Post-doctoral degree on Biochemical Markers in Depression. Clinical
Research Associate in psychiatry in University of Cambridge 1986 – 1990.
Reader in Psychological Medicine in University of Wales College of
Medicine, Director of the North Wales Department of Psychological Medicine
from 1992. Former Secretary of the British Association for
Psychopharmacology. Author of over 120 peer reviewed articles and 12
books, including the reference history of the antidepressants – The
Antidepressant Era, Harvard University Press – and The Creation of
Psychopharmacology, Harvard University Press. Other books include a
three volume series of interviews – The Psychopharmacologists Volumes
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